synthesis and catalytic functionalization of biologically active indoles

Synthesis of Potential 5-HT 6 Receptor Ligands
ringe. The reaction mixture was stirred for 2 h at –30 °C. The dark
violet solution was charged with NH4Cl carefully until all sodium
was destroyed. After 1 h water was added to the reaction mixture,
extracted with dichloromethane and dried with Mg2SO4. The solvent
was removed and the crude product was cleaned by column
chromatography (eluent: ethyl acetate gradient 5–20 % in hexane).
The product was obtained as brown oil with a yield of 130 mg
(20%). 1H NMR (500.13 MHz, CDCl3): δ = 7.00 (d, J = 8.5 Hz, 1
H), 6.78 (d, J = 2.2 Hz, 1 H), 6.60 (dd, J = 8.5, J = 2.2 Hz, 1 H),
3.54 (s, 3 H), 2.93 (br., 2 H, NH2), 2.25 (s, 3 H), 1.07 (s, 9 H), 0.15
(s, 6 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 137.7 (Cq), 129.5
(Cq), 129.4 (Cq), 123.2 (Cq), 122.2 (Cq), 111.5, 108.9, 102.8, 29.4,
25.9, 18.2 (Cq), 9.2, –4.2 ppm. MS (EI, 70 eV): m/z (%) = 292 (19),
290 (100) [M + ], 233 (25), 218 (6), 192 (7), 175 (5), 160 (14), 159
(13), 73 (5).. HRMS: calcd. for C16H26N2OSi: 290.18089; found
290.180559. FTIR (Nujol): ν˜ = 3446, 2952, 2923, 2854, 1844, 1648,
1559, 1506, 1457, 1419, 1376, 1318, 1251, 1160, 1066, 891, 778
cm –1 .
Compounds 8a–i. General Procedure for the Sulfonylation of 5-
Amino-3-(silanyloxy)indole Derivatives: Under argon atmosphere
the indole derivative (1 mmol) and the arylsulfonyl chloride
(2 mmol) were dissolved in triethylamine (5 mL) and heated to
40 °C for 2 h. After the reaction was complete by TLC control, the
solvent was removed in vacuo. The product was isolated by column
chromatography with hexane/ethyl acetate (10:1) as a solid material.N-Benzyl-N-[3-(tert-butyldimethylsilanyloxy)-1,2-dimethyl-1Hindol-5-yl]naphthalene-2-sulfonamide
(8a): 1H NMR (500.13 MHz,
CDCl3): δ = 8.27 (d, J = 1.7 Hz, 1 H), 7.91 (d, J = 8.7 Hz, 1 H),
7.91–7.87 (m, 2 H), 7.71 (dd, J = 8.7, J = 1.7 Hz, 1 H), 7.63, 7.57
(2 ddd, 2 H), 7.27–7.24 (m, 2 H), 7.21–7.14 (m, 3 H), 7.01 (d, J =
8.8 Hz, 1 H), 6.95 (d, J = 2.0 Hz, 1 H), 6.71 (dd, J = 8.8, J =
2.0 Hz, 1 H), 4.87 (s, 2 H), 3.51 (s, 3 H), 2.22 (s, 3 H), 0.88 (s, 9
H), –0.16 (s, 6 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 136.6
(Cq), 136.6 (Cq), 134.8 (Cq), 132.8 (Cq), 132.2 (Cq), 130.4 (Cq),
129.6 (Cq), 129.3, 128.9, 128.8, 128.7, 128.5, 128.2, 127.8, 127.4,
127.2, 123.5 (Cq), 123.3, 122.2, 121.4 (Cq), 118.0, 108.5, 56.2
(CH2), 29.5, 25.7, 18.0 (Cq), 9.1, –4.5 ppm. MS (EI, 70 eV): m/z
(%) = 571 (16), 570 (38) [M + ], 380 (46), 379 (99), 378 (15), 277 (6),
276 (5), 205 (28), 204 (5), 203 (31), 191 (5), 93 (9), 92 (13), 91
(100), 78 (10), 77 (21), 74 (11), 73 (96), 57 (38). HRMS: calcd. for
C33H38N2O3SSi: 570.236511; found 570.23669. FTIR (ATR): ν˜ =
3057, 3301, 2956, 2929, 2854, 1337, 1321, 1247, 1156, 1131, 1077,
820, 807, 786, 754, 699, 666 cm –1 .
Naphthalene-2-sulfonamide 8b: 1H NMR (500.13 MHz, CDCl3): δ
= 8.21 (d, J = 1.8 Hz, 1 H), 7.89–7.85 (m, 3 H), 7.65 (dd, J = 8.8,
J = 1.8 Hz, 1 H), 7.61, 7.55 (2m, 2 H), 7.09 (d, J = 8.8 Hz, 1 H),
7.01 (d, J = 2.2 Hz, 1 H), 6.84 (dd, J = 8.8, J = 2.2 Hz, 1 H), 3.66
(t, J = 7.0 Hz, 2 H), 3.58 (s, 3 H), 2.26 (s, 3 H), 1.45–1.18 (m, 8
H), 0.89 (s, 9 H), 0.84 (t, J = 7.3 Hz, 3 H), –0.10 (s, 6 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 138.2 (Cq), 136.3 (Cq), 134.6 (Cq),
132.8 (Cq), 130.4 (Cq), 129.7 (Cq), 129.3, 128.7, 127.8, 128.7,
128.3, 127.1, 123.7 (Cq), 123.3, 122.1, 121.5 (Cq), 117.5, 108.6, 51.7
(CH2), 31.4 (CH2), 28.3 (CH2), 26.1 (CH2), 22.5 (CH2), 29.5, 25.6,
17.9 (Cq), 13.9, 9.1, –4.5 ppm. MS (EI, 70 eV): m/z (%) = 565 (18),
373 (100), 304 (4), 303 (15), 302 (4), 243 (6), 185 (5), 160 (8), 128
(10), 127 (8), 83 (11), 82 (6), 73 (12), 57 (17), 55 (18). HRMS: calcd.
for C32H44N2O3SSi: 564.28364; found 564.283310. FTIR (KBr): ν˜
= 3444, 3060, 2958, 2929, 2852, 1732, 1487, 1464, 1377, 1337, 1249,
1163, 1129, 1074, 891, 839, 813, 782, 749, 666, 616, 544 cm –1 .
Naphthalene-2-sulfonamide 8c: 1H NMR (300.13 MHz, CDCl3): δ
= 8.27 (d, J = 1.5 Hz, 1 H), 7.83 (m, 3 H), 7.69 (dd, J = 8.6, J =
1.9 Hz, 1 H), 7.61–7.57 (m, 1 H), 7.55–7.51 (m, 1 H), 7.04–7.01 (m,
2 H), 6.85 (dd, J = 8.8, J = 2.0 Hz, 1 H), 6.49 (br. s, 1 H, NH),
3.53 (s, 3 H), 2.22 (s, 3 H), 0.93 (s, 9 H), –0.12 (s, 6 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 136.2 (Cq), 134.9 (Cq), 132.3 (Cq),
132.1 (Cq), 130.3 (Cq), 129.3, 129.1, 128.8, 128.6, 127.8, 127.2,
126.6 (Cq), 123.9 (Cq), 122.7, 121.6 (Cq), 118.6, 113.6, 108.9, 29.5,
25.7, 18.0 (Cq), 9.2, –4.5 ppm. MS (EI, 70 eV): m/z (%) = 481 (23),
480 (70) [M + ], 291 (6), 290 (23), 289 (100), 232 (5), 231 (5), 161 (2),
160 (7), 159 (5), 129 (2), 128 (7), 127 (8), 79 (3), 78 (5), 77 (11), 57
(5), 56 (4). HRMS: calcd. for C26H32N2O3SSi: 480.18974; found
480.189326. FTIR (ATR): ν˜ = 3237, 3056, 2930, 2857, 1376, 1331,
1273, 1247, 1161, 1153, 1130, 1074, 895, 836, 816, 795, 777, 743,
675 cm –1 .
Naphthalene-2-sulfonamide 8d: 1H NMR (300.13 MHz, CDCl3): δ
= 8.19 (d, J = 1.5 Hz, 1 H), 7.89–7.83 (m, 3 H), 7.64–7.51 (m, 3
H), 7.30–7.12 (m, 4 H), 7.02 (d, J = 2.1 Hz, 1 H), 6.90 (dd, J =
8.7, J = 2.1 Hz, 1 H), 3.93 (m, 2 H), 3.62 (s, 3 H), 2.80 (m, 2 H),
2.28 (s, 3 H), 0.89 (s, 9 H), –0.11 (s, 6 H) ppm. 13CNMR (75.5 MHz, CDCl3): δ = 138.5 (Cq), 136.1 (Cq), 134.7 (Cq), 133.0
(Cq), 132.1 (Cq), 130.4 (Cq), 129.6 (Cq), 129.3, 128.9, 128.8, 128.7,
128.4 (2�), 127.7, 127.2, 126.4, 123.9 (Cq), 123.3, 122.3, 121.6
(Cq), 117.5, 108.8, 53.2 (CH2), 35.2 (CH2), 29.6, 25.6, 18.0 (Cq),
9.2, –4.5 ppm. MS (EI, 70 eV): m/z (%) = 585 (15), 584 (35) [M + ],
394 (12), 393 (28), 392 (2), 303 (34), 302 (100), 246 (7), 245 (17),
218 (4), 217 (12), 216 (3), 188 (4), 187 (10), 128 (13), 127 (13), 73
(16). HRMS: calcd. for C34H40N2O 3SSi: 584.25234; found
584.25293. FTIR (ATR): ν˜ = 3083, 3061, 3026, 2958, 2930, 2855,
1331, 1249, 1152, 1129, 1072, 937, 890, 833, 817, 783, 750, 692, 665
cm –1 .
Naphthalene-2-sulfonamide 8e: 1H NMR (300.13 MHz, CDCl3): δ
= 8.17 (d, J = 1.7 Hz, 1 H), 7.87–7.82 (m, 3 H), 7.61–7.52 (m, 3
H), 7.11 (d, J = 8.6 Hz, 1 H), 7.10–7.05 (m, 2 H), 7.00 (d, J =
2.0 Hz, 1 H), 6.95–6.90 (m, 2 H), 6.84 (dd, J = 8.5, J = 2.0 Hz, 1
H), 3.90 (m, 2 H), 3.59 (s, 3 H), 2.76 (m, 2 H), 2.26 (s, 3 H), 0.88
(s, 9 H), –0.11 (s, 6 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
161.6 (d, J = 244 Hz, Cq), 136.0 (Cq), 134.7 (Cq), 134.1 (d, J =
3.2 Hz, Cq), 132.9 (Cq), 132.1 (Cq), 130.4 (Cq), 130.3 (d, J =
7.8 Hz), 129.5 (Cq), 129.2, 128.8, 128.8, 128.4, 127.8, 127.2, 123.9
(Cq), 123.2, 122.1, 121.6 (Cq), 117.6, 115.2 (d, J = 21.5 Hz), 108.8,
53.1 (CH2), 34.3 (CH2), 29.6, 25.6, 17.9 (Cq), 9.1, –4.5 ppm. MS
(EI. 70 eV): m/z (%) = 603 (14), 602 (34) [M + ], 413 (2), 412 (8), 411
(18), 304 (8), 303 (32), 302 (100), 246 (5), 245 (13), 217 (7), 216 (2),
187 (7), 186 (2), 185 (5), 128 (7), 127 (7), 109 (5), 73 (9). HRMS:
calcd. for C34H39FN2O3SSi: 602.24292; found 602.243034. FTIR
(ATR): ν˜ = 3064, 3042, 2959, 2932, 2855, 1509, 1337, 1248, 1219,
1152, 1130, 1106, 1075, 938, 891, 855, 835, 815, 781, 749, 665 cm –1 .
6-Chloroimidazo[2,1-b]thiazole-5-sulfonamide 8f: 1HNMR (300.13 MHz, CDCl3): δ = 7.07 (d, J = 2.0 Hz, 1 H), 6.91 (d, J =
4.5 Hz, 1 H), 6.88 (d, J = 8.6 Hz, 1 H), 6.60 (dd, J = 8.6, J =
2.0 Hz, 1 H), 6.51 (d, J = 4.5 Hz, 1 H), 3.66 (t, J = 7.0 Hz, 2 H),
3.44 (s, 3 H), 2.24 (s, 3 H), 1.36–1.01 (m, 8 H), 0.90 (s, 9 H), 0.70
(t, J = 7.0 Hz, 3 H), –0.09 (s, 6 H) ppm. 13C NMR (75.5 MHz,
CDCl3): δ = 149.1 (Cq), 137.2 (Cq), 132.9 (Cq), 130.4 (Cq), 128.4
(Cq), 124.1 (Cq), 121.6 (Cq), 120.7, 120.6, 119.4 (Cq), 118.2, 113.0,
108.8, 52.1 (CH2), 31.4 (CH2), 29.6, 28.2 (CH2), 26.1 (CH2), 25.8,
22.5 (CH2), 18.1 (Cq), 14.0, 9.2, –4.3 ppm. MS (EI, 70 eV): m/z (%)
= 595 (12), 594 (34) [M + ], 531 (4), 530 (11), 495 (10), 494 (12), 424
(19), 423 (8), 422 (38), 375 (18), 374 (76), 373 (100), 304 (12), 303
(52), 302 (9), 290 (13), 262 (15), 158 (14), 73 (31). HRMS: calcd.
for C27H39ClN4O3S2Si: 594.19159; found 594.192313. FTIR (KBr):
ν˜ = 3150, 3117, 2954, 2925, 2852, 2709, 2479, 1842, 1736, 1486,
1455, 1360, 1324, 1269, 1248, 1178, 1133, 1084, 1068, 946, 890,
839, 807, 781, 727, 668, 619 cm –1 .
Eur. J. Org. Chem. 2008, 5425–5435 © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org 5433